The manner in which different pharmacological agents utilize or depend upon cellular Ca ions sites or stores for the maintenance of contractive tone and the initiation of contractile responses in isolated vascular smooth muscle systems will be examined. The effects of norepinephrine, angiotensin II, potassium and histamine on tension, ionic concentrations and Ca 45 distribution and movements in the presence and absence of Ca ions depletion and of Ca ions antagonists such as procaine and lanthanum (and other selected rare earth ions) will be delineated. Conventional techniques will be employed for measurement of isometric tension responses, for Ca 45 uptake and rapid washout, and for total Ca ions, Na and K ions concentrations. Experiments will be designed to elucidate the manner in which different vascular preparations depend upon cellular Ca ions stores as well as Ca 45 uptake and retention for maintenance of tone and responsiveness to vasoactive agents. This information could provide a basis for evaluation of ideas concerning the mechanisms by which membrane-bound Ca ions is involved in events leading to alterations in contractile tone. In this regard, systematic comparisons will be attempted for patterns of Ca ions utilization in rabbit aorta and in dog femoral and mesenteric arteries as well as in corresponding preparations obtained from monkeys and baboons. Emphasis will also be placed upon rigorous examination of the use of La ions as a specific Ca ions antagonist in these vascular systems and upon development of other types of Ca ions antagonists. Thus, this investigation would provide information about the cellular mechanisms of action of a number of pharmacological agents in a variety of isolated vascular smooth muscle systems. A comparative approach of this type should help answer some general questions about the sequence of events important in initiation and maintenance of tension in mammalian vascular smooth muscle.